Diffusion tensor imaging identifies changes in normal-appearing white matter within the epileptogenic zone in tuberous sclerosis complex

PURPOSE To evaluate diffusion tensor imaging (DTI) indices of (i) cortical tubers and (ii) normal-appearing subcortical white matter adjacent to cortical tubers within the epileptogenic zone and non-epileptogenic zone. METHODS Twelve children with tuberous sclerosis complex underwent MRI, DTI and magnetoencephalography (MEG). Regions of interest (ROIs) were placed within cortical tubers and normal-appearing subcortical white matter adjacent to cortical tubers within MEG identified epileptogenic zone and non-epileptogenic zone. Fractional anisotropy (FA), mean diffusivity (MD), axial diffusivity (lambda(parallel)) and radial diffusivity (lambda(perpendicular)) were calculated. RESULTS 26 out of 104 cortical tubers were in the epileptogenic zone. FA of cortical tubers in the epileptogenic zone was significantly lower than non-epileptogenic zone (p=0.015). There were no significant differences between MD (p=0.896), lambda(parallel) (p=0.672) and lambda(perpendicular) (p=0.651) of cortical tubers in the epileptogenic and non-epileptogenic zone. In normal-appearing subcortical white matter within the epileptogenic zone, FA was lower (p=0.001) and lambda(perpendicular) (p=0.011) was higher than non-epileptogenic zone. There were no significant differences between MD (p=0.110) and lambda(parallel) (p=0.735) of normal-appearing subcortical white matter within the epileptogenic and non-epileptogenic zone. CONCLUSION DTI changes in normal-appearing white matter within the epileptogenic zone could represent abnormal white matter related to MRI-occult dysplastic cortex or ictal/interictal activity.

[1]  Shu-Wei Sun,et al.  Diffusion tensor imaging detects and differentiates axon and myelin degeneration in mouse optic nerve after retinal ischemia , 2003, NeuroImage.

[2]  H. Northrup,et al.  Tuberous Sclerosis Complex Consensus Conference: Revised Clinical Diagnostic Criteria , 1998, Journal of child neurology.

[3]  O. Muzik,et al.  Epilepsy Surgery Outcome in Children With Tuberous Sclerosis Complex Evaluated With α-[11C]Methyl-L-Tryptophan Positron Emission Tomography (PET) , 2005, Journal of child neurology.

[4]  G. Klem,et al.  Epileptogenicity of Focal Malformations Due to Abnormal Cortical Development: Direct Electrocorticographic–Histopathologic Correlations , 2003, Epilepsia.

[5]  H. Hoshi,et al.  Magnetic resonance spectroscopy of tubers in patients with tuberous sclerosis , 2000, Acta neurologica Scandinavica.

[6]  Jeroen van der Grond,et al.  Diffusion-weighted magnetic resonance imaging and identification of the epileptogenic tuber in patients with tuberous sclerosis. , 2003, Archives of neurology.

[7]  H. Otsubo,et al.  Characterizing Magnetoencephalographic Spike Sources in Children with Tuberous Sclerosis Complex , 2005, Epilepsia.

[8]  G. Mathern,et al.  FDG‐PET/MRI Coregistration and Diffusion‐Tensor Imaging Distinguish Epileptogenic Tubers and Cortex in Patients with Tuberous Sclerosis Complex: A Preliminary Report , 2006, Epilepsia.

[9]  H. Karakas,et al.  Diffusion weighted MR findings of brain involvement in tuberous sclerosis. , 2006, Diagnostic and interventional radiology.

[10]  M. Duchowny,et al.  The localizing value of ictal SPECT in children with tuberous sclerosis complex and refractory partial epilepsy. , 1999, Epileptic disorders : international epilepsy journal with videotape.

[11]  E. Pestana,et al.  Identification of candidates for epilepsy surgery in patients with tuberous sclerosis , 2005, Neurology.

[12]  M. Calcagnotto,et al.  Neocortical hyperexcitability in a human case of tuberous sclerosis complex and mice lacking neuronal expression of TSC1 , 2007, Annals of neurology.

[13]  H. Chugani,et al.  Characteristics of Abnormal Diffusivity in Normal-Appearing White Matter Investigated with Diffusion Tensor MR Imaging in Tuberous Sclerosis Complex , 2007, American Journal of Neuroradiology.

[14]  F. Tamanoi,et al.  Loss of tuberous sclerosis complex 1 (Tsc1) expression results in increased Rheb/S6K pathway signaling important for astrocyte cell size regulation , 2004, Glia.

[15]  F. DiMario.  Brain Abnormalities in Tuberous Sclerosis Complex , 2004, Journal of child neurology.

[16]  O. Muzik,et al.  Multimodality imaging for improved detection of epileptogenic foci in tuberous sclerosis complex , 2000, Neurology.

[17]  Hiroshi Otsubo,et al.  Subcortical alterations in tissue microstructure adjacent to focal cortical dysplasia: detection at diffusion-tensor MR imaging by using magnetoencephalographic dipole cluster localization. , 2009, Radiology.

[18]  H. Onda,et al.  Heterozygosity for the tuberous sclerosis complex (TSC) gene products results in increased astrocyte numbers and decreased p27-Kip1 expression in TSC2+/− cells , 2002, Oncogene.

[19]  Susan Blaser,et al.  Evaluation of Subcortical White Matter and Deep White Matter Tracts in Malformations of Cortical Development , 2007, Epilepsia.

[20]  W. Kaiser,et al.  Diffusion tensor imaging in children and adolescents with tuberous sclerosis , 2005, Pediatric Radiology.

[21]  H. Otsubo,et al.  Characterizing magnetic spike sources by using magnetoencephalography-guided neuronavigation in epilepsy surgery in pediatric patients. , 2005, Journal of neurosurgery.

[22]  F. Garaci,et al.  Increased brain apparent diffusion coefficient in tuberous sclerosis. , 2004, Radiology.

[23]  P. Basser,et al.  MR diffusion tensor spectroscopy and imaging. , 1994, Biophysical journal.

[24]  C. Wasterlain,et al.  Electroconvulsive seizures in the immature rat adversely affect myelin accumulation , 1982, Experimental Neurology.

[25]  Koji Iida,et al.  Three-dimensionally Reconstructed Magnetic Source Imaging and Neuronavigation in Pediatric Epilepsy: Technical Note , 2004, Neurosurgery.

[26]  P. Basser,et al.  Diffusion tensor MR imaging of the human brain. , 1996, Radiology.

[27]  R Sankar,et al.  Magnetic source imaging localizes epileptogenic zone in children with tuberous sclerosis complex , 2006, Neurology.

[28]  T. Rasmussen,et al.  Surgical treatment of epilepsy in tuberous sclerosis , 1998, Neurology.

[29]  P. Basser,et al.  Toward a quantitative assessment of diffusion anisotropy , 1996, Magnetic resonance in medicine.

[30]  M. Duchowny,et al.  Epilepsy Surgery in Children with Tuberous Sclerosis Complex: Presurgical Evaluation and Outcome , 2000, Epilepsia.

[31]  Mirela V. Simon,et al.  Are cortical tubers epileptogenic? Evidence from electrocorticography , 2009, Epilepsia.

[32]  I. Izbudak,et al.  Magnetic resonance imaging and diffusion-weighted imaging of normal-appearing white matter in children and young adults with tuberous sclerosis complex , 2009, Neuroradiology.

[33]  John Russell,et al.  Dysmyelination Revealed through MRI as Increased Radial (but Unchanged Axial) Diffusion of Water , 2002, NeuroImage.

[34]  S. Peng,et al.  Cerebral diffusion tensor images in children with tuberous sclerosis: a preliminary report , 2004, Pediatric Radiology.

[35]  Geertjan Huiskamp,et al.  Identification of the Epileptogenic Tuber in Patients with Tuberous Sclerosis: A Comparison of High‐resolution EEG and MEG , 2006, Epilepsia.

[36]  W. Qin,et al.  Cerebral diffusion tensor imaging in tuberous sclerosis. , 2009, European journal of radiology.

[37]  S. Seri,et al.  Topical Review: Intractable Seizures in Tuberous Sclerosis Complex: From Molecular Pathogenesis to the Rationale for Treatment , 2004, Journal of child neurology.